1. Field of the Invention
The present invention relates generally to compositions, methods for treatment, and methods for preparation of injectable collagen implant materials for soft tissue augmentation. More particularly, the present invention relates to high concentration collagen compositions that have been homogenized to enhance injectability.
The use of both cross-linked and non-cross-linked collagen compositions for soft tissue repair and augmentation is known. The preparation and use of non-cross-linked collagen compositions is described in U.S. Pat. No. 3,949,073, the disclosure of which is fully incorporated herein by reference. A commercial product incorporating non-cross-linked collagen at a concentration of 65 mg/ml is available from Collagen Corporation, Palo Alto, Calif., under the tradename Zyderm II. The preparation and use of cross-linked collagen compositions is described in U.S. Pat. No. 4,582,640, the disclosure of which is fully incorporated herein by reference. A commercial product incorporating cross-linked collagen at a concentration of 35 mg/ml is available from Collagen Corporation, Palo Alto, Calif., under the tradename Zyplast.
The use of both cross-linked and non-cross-linked collagen compositions for soft tissue repair and augmentation has been limited by a lack of "persistence," where persistence is defined as the tendency for the implanted collagen to form a cohesive mass and resist migration from an injection site. Previous injectable collagen compositions have also suffered from syneresis where the liquid component of the composition (typically a gel) separates during or after injection, resulting in a non-uniform consistency in the implant.
One approach for improving persistence and reducing syneresis might be to increase the collagen concentration in the composition used for soft tissue augmentation. Heretofore, the use of high concentration collagen compositions has been shown to be ineffective due to the difficulty in introducing the composition to the treatment site. Most commonly, collagen compositions are introduced as aqueous suspensions through a fine gauge needle to the tissue site of interest. Injection of high concentration collagen compositions is problematic. The use has been further discouraged by a perception that implants formed from high concentration collagens will calcify and harden over time. Hardened collagen implants are generally unacceptable for soft tissue implantation. For these reasons, any benefits which may derive from the use of high concentration collagen compositions remain speculative.
It would thus be desirable to provide improved collagen compositions, improved methods for preparing collagen compositions, and improved methods for therapeutically introducing such collagen compositions to a treatment site of interest. In particular, it would be desirable to provide collagen compositions having enhanced persistence after being introduced in vivo to a soft tissue treatment site within a patient. Even more particularly, it would be desirable to provide compositions having high collagen concentrations which remain readily injectable so that they can be introduced using fine gauge needles to the soft tissue site. In addition to the improved persistence, the collagen composition should be stable, i.e., undergo no significant changes (such as syneresis) in situ; be tough and elastic, i.e., be capable of bearing loads without undergoing excessive or permanent deformation; be non-toxic and well-tolerated by the body, i.e., produce no or tolerable levels of immune and inflammatory response; and be intrudable, i.e., form a relatively dispersed, irregular-shaped mass within the tissue where it has been introduced. It will be appreciated, of course, that the compositions and methods of the present invention while meeting at least some of these objectives, will not necessarily meet all of these objectives in every embodiment.
2. Description of the Background Art
U.S. Pat. Nos. 3,949,073 and 4,582,640, have been described above. U.S. Pat. No. 4,803,075, describes injectable cross-linked collagen compositions which are combined with a fluid lubricant to enhance intrudability. U.S. Pat. No. 4,424,208, describes a collagen composition including cross-linked collagen and reconstituted collagen fibers having enhanced persistence but limited extrusion and intrusion properties. U.S. Pat. No. 4,582,640, teaches that injectability of low concentration collagen compositions can be enhanced by forcing a suspension of the collagen fibers through a screen of defined pore size. It is suggested that the screen breaks up fibrillar aggregates that may be in the suspension to achieve a more uniform fiber size distribution. McPherson et al. (1988) J. Dermatol. Surg. Oncol. 14 (Suppl. 1) 7, describes improved persistence with non-homogenized 65 mg/ml non-cross-linked collagen (Zyderm II).